Excretion Ratio Research Articles

Intraspecific competition reduces the quantity of excreted nutrients in tadpoles

Anuran larvae can form the largest animal biomass seasonally in freshwater environments, yet, they are still one of the least-studied taxa in terms of nutrient regeneration. The present study tested whether sympatric tadpoles regenerate nutrients at similar rates and ratios, and whether increased intraspecific competition (hereafter ‘competition’) alters patterns of excretion. We quantified rates and ratios of excretion (dissolved nitrogen (N) from ammonia, phosphorus (P) from total dissolved P, and N:P ratio) in three pond-dwelling Japanese tadpoles (Pelophylax nigromaculatus, Rhacophorus schlegelii, Hyla japonica), and tested the effect of competition on excretion in Pelophylax nigromaculatus and Rhacophorus arboreus. The three co-occurring species regenerated nutrients at different rates and ratios; H. japonica excreted nutrients and produced faecal pellets at the lowest rates. Inside field enclosures, increasing tadpole density reduced the quantity but not the quality of excretion by the tadpoles, suggesting higher nutrient sequestration, likely to maintain a stoichiometrically balanced growth under limited resources. Differences in rates and ratios of excretion have previously been shown to have various effects on community structure by affecting primary productivity, highlighting the importance of species identity and interactions on ecosystem function.

Tolerability, Safety, Pharmacokinetics and Drug Interaction of Cefotaxime Sodium-Tazobactam Sodium Injection (6:1) Following Single and Multiple Intravenous Doses in Chinese Healthy Subjects.

PurposeTo evaluate the tolerability, safety, pharmacokinetics and drug interaction of cefotaxime sodium–tazobactam sodium injection (6:1) in Chinese healthy subjects. The results of the safety and pharmacokinetic studies supported further clinical trials.MethodA randomized, single-blind, ascending dose, placebo-controlled, single-center study was conducted. Sixty healthy subjects (38 males, 22 females) participated in this study. For the single-dose part, 0.47, 1.17, 2.34, 3.51, and 4.68 g of cefotaxime sodium–tazobactam sodium injection (6:1) was administered. For the multiple-dose part, the subjects were administered 2.34 and 3.51 g cefotaxime sodium–tazobactam sodium injection (6:1) three times a day for 7 consecutive days. For the drug interaction part, the subjects received 2.0 g cefotaxime sodium and 0.34 g tazobactam sodium alone and in combination.ResultsMost adverse events and adverse drug reactions were mild. Moderate rash was considered a serious adverse event because of prolongation of hospitalization. The main pharmacokinetic parameters of cefotaxime and tazobactam had no significance difference between the 1.17, 2.34, and 3.51 g dose cohorts and between genders. There was no difference in trough concentrations on days 6, 7, and 8. The RC max and RAUC were (0.921 ± 0.070) and (0.877 ± 0.057) for cefotaxime, and (0.913 ± 0.046) and (0.853 ± 0.060) for tazobactam, respectively. Following the administration of cefotaxime and tazobactam alone and in combination, the 90% confidence intervals of the geometric mean ratios for C max and AUC were within the predetermined range of 80–125%. In the single-dose part, the renal cumulative excretion ratios were (51.7 ± 6.2)% for cefotaxime, and (84.3 ± 8.1)% for tazobactam. There was no significant difference in the maximum excretion rates and cumulative excretion ratios for cefotaxime and tazobactam, alone or in combination.ConclusionsCefotaxime sodium–tazobactam sodium injection (6:1) was well-tolerated at doses of 0.47 to 4.68 g. The pharmacokinetics of cefotaxime and tazobactam were reported as linear over a dose range of 1.17–3.51 g. Cefotaxime was partially excreted via urine, whereas tazobactam was mainly excreted via urine. There was no significant accumulation after administration over 7 consecutive days. The pharmacokinetics and excretion of cefotaxime and tazobactam were not affected by the co-administration of cefotaxime–tazobactam.

Impaired Daytime Urinary Sodium Excretion Impacts Nighttime Blood Pressure and Nocturnal Dipping at Older Ages in the General Population.

The circadian rhythm of urinary sodium excretion is related to the diurnal blood pressure regulation (BP) and the nocturnal dipping pattern. The renal sodium excretion expressed as daytime/nighttime ratio impacts BP, but a limited number of studies have investigated this topic to date. In this cross-sectional study, we aimed to investigate the impact of different daily patterns of sodium excretion (comparing low with high ratios) on BP and nocturnal dipping and to explore the relationship with age. Twenty-four-hour ambulatory BP monitoring and daytime and nighttime urinary sodium collections were used to assess 1062 subjects in Switzerland. Analyses were performed according to the day/night urinary sodium excretion ratio quartiles (Q1–Q4) and by age group (≤50 and ≥50 years). Subjects in Q1 can be considered low excretors of sodium during the daytime since the rate of sodium excretion during the daytime was 40% lower than that of subjects in Q4. Quartiles of the day/night urinary sodium excretion ratio showed that subjects in Q1 were 7 years older and had respectively 6 and 5 mmHg higher nighttime systolic and diastolic BP and a higher nocturnal dipping compared with subjects in Q4 (p-value ≤0.001). Associations found were significant only for subjects older than 50 years (all p < 0.05). The present results suggest that a decreased capacity to excrete sodium during daytime is more prevalent as age increases and that it impacts nighttime blood pressure and nocturnal dipping in older subjects.

Probable role of ablation of cerebral ganglia and injection of its extracts on O:N ratio of &lt;em&gt;Lamellidens corrianis &lt;/em&gt;during summer season

Amongst invertebrates, molluscs show great variability in their nervous system ranging from primitive arrangement in Chitons to the complex mass of fused ganglia forming the ‘brain’ of cephalopods. Most of the effector organs used for pharmacological or physiological experiments. The neurosecretory cells (NSCs) with their combination of neuronal and glandular capabilities are perfectly suited to translate a neuronal input into the hormonal output best suited to long-term process. In this capacity, the NSCs may produce hormones, which act directly upon the peripheral target or it may exert its effect indirectly by influencing the activity of other non-neural, endocrine organs. Neurosecretory cells have been detected in the cerebral, pedal and visceral ganglia of Lamellidens corrianus. The distribution and biology of freshwater bivalve like Lamellidens corrianus is influenced by local ecological factors (like temperature, pH, inorganic salts, type of soil etc.), water flow system and presence of micro-organisms, teleost fishes and seasonal variations in these parameters. Nitrogenous excretory changes which include ammonia in these molluscs is also influenced by these local ecological factors in which temperature is plays very crucial role. It is well known fact that the high stress conditions during drought or severe winter conditions have been conquered by several lineage of gastropods and sand bivalves and their ability to enter the resistant or dormant stages (low food) protein catabolism increased. Present investigation deals with the oxygen consumption and ammonia excretion ratio of these freshwater pelecypode Lamellidens corrianus. Study on Lemellidens corrianus directed in understanding the different behavioral and physiological aspects after cerebral ganglia removal and injection of their extracts revealed significant changes during summer (April-May).

Biomarkers of Environmental Enteric dDsfunction (EED) Predict Growth and Recovery Among Children with Moderate Acute Malnutrition (MAM) in Sierra Leone

Abstract Objectives The objectives of the study were to 1) develop an EED score using fecal host mRNA transcripts, 2) compare three EED biomarkers, and 3) examine associations between EED biomarkers and growth outcomes and recovery from MAM. Methods In a study nested within a supplementary feeding program for children 6–59 months of age with MAM in Sierra Leone, EED was assessed in all children enrolled using: 1) lactulose: mannitol (L: M) test (n = 422), 2) fifteen host fecal mRNA transcripts (n = 441), and 3) host fecal proteins [alpha-1-anti trypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)] (n = 200). Data were also collected on anthropometry and z scores computed for length-for-age (LAZ), and weight-for-length (WLZ). Length and weight gain were assessed over 2 weeks and recovery from MAM was defined as mid-upper arm circumference ≥12.5 cm. Factor analysis was used to identify EED scores using the mRNA transcripts and mixed effects regression was conducted to test for associations. Results The fifteen host fecal mRNA transcripts clustered into three scores using factor analysis (Eigen value &amp;gt;1). These were termed the Gut Inflammation (GI) score (Eigen value = 5.55), Gut Structure (GS) score (Eigen value = 2.48), and Gut Defense (GD) score (Eigen value = 2.22). We found agreement between the GI score and MPO (P &amp;lt; 0.001), the GS score and AAT (P = 0.001), and between AAT and L: M excretion ratio (P = 0.036). The GD score was negatively associated with %L (P &amp;lt; 0.001). A lower LAZ was associated with higher inflammation (GI score, P = 0.014). A lower length gain was associated with higher permeability (AAT, P = 0.001). A lower WLZ was associated with higher inflammation (GI score, P = 0.021) and higher permeability (GS score, P = 0.002). A lower weight gain was associated with lower gut defense (GD score, P = 0.044) and higher inflammation (MPO, P = 0.002). High gut defense (GD score, P = 0.011) and low permeability (AAT, P = 0.007) predicted recovery from MAM. Conclusions Fifteen mRNA transcripts clustered into three scores with clusters reflecting inflammation, permeability and gut defense. These were variably correlated with the L: M test and host fecal proteins but seemed to measure the same characteristics of EED. Markers of inflammation, permeability, and gut defense were associated with growth outcomes, and predicted recovery from MAM. Funding Sources U.S. Agency for International Development (USAID).

SAT-377 Case Series of Ectopic Parathyroid Gland

The prevalence of mediastinal parathyroid adenoma is unknown. Embryological origin and more extensive aberrant migration of the parathyroid glands result in ectopic glands found in the mediastinum. We report herein 4 cases of ectopic parathyroid adenoma causing primary hyperparathyroidism from three public hospitals in MalaysiaCase 1.A 70 year old lady with underlying diabetes mellitus, hypertension, chronic immune thrombocytopenic purpura and liver cirrhosis presented with incidental asymptomatic hypercalcemia during an admission for pneumonia. Her blood results revealed high corrected calcium of 2.93 mmol/L (2.02-2.60) and a low phosphate of 0.66 (0.81-1.45) mmol/L with an unsuppressed intact parathyroid hormone (iPTH) of 14.56 pmol/L (1.6-6.9). She had an equivocal urinary calcium excretion ratio of 0.01. Her bone mineral density confirmed severe osteoporosis at distal radius and neck of femur with a Tscore of -3.6 and -3.1 respectively. A hyperfunctioning ectopic parathyroid gland was seen in the Technetium Sestamibi scan which corelates with a mediastinal lymphadenopathy on CECT. The largest node measured 1.6 x 1.2 cm. Parathyroid gland was confirmed on HPE of the video-assisted-thoracoscopic surgical (VATS) excision of the mediastinal mass. Intraoperative iPTH (ioPTH) serially reduced from 8.87 to 1.94 to 1.03 pmol/L and she maintained a serum calcium levels of 2.4 mmol/L post surgery. She did not require any calcium or vitamin D supplementation. Case 2. A 36 year old male presented with generalized body weakness secondary to hypokalemia. His calcium was 3.07 mmol/l, phosphate 0.64 mmol/l and iPTH 11.53 pmol/L. Increase Technetium uptake seen at mediastinum. Post operatively, calcium normalized and remained stable 1 year later. Case 3.47 year old female presented with acute gallstone pancreatitis complicated with a pancreatic pseudocyst. She was found to have hypercalcemia of 2.77 mmol/L, phosphate 0.70 mmol/l and iPTH 21.87 pmol/L. Sestamibi scan revealed hyperfunctiong parathyroid tissue posterior to the left thyroid lobe and in the mediastinum. She is awaiting surgery. Case 4.Another asymptomatic 47 year old male who has history of post Radioactive-iodine hypothyroidism had an incidental finding of serum calcium of 2.69-2.84 mmol/L, phosphate 0.71-0.91 mmol/L and iPTH 9.89 pmol/L with urinary calcium excretion ratio of 0.019. His Sestamibi scan showed uptake at the superior mediastinum. Ectopic parathyroid gland is rarely encountered. With the advent of Technetium-Sestamibi scintigraphy, ectopic parathyroid adenoma can be localized easily. However, surgery poses a challenge due the location of the adenoma which may occasionally be near large vascular structures in the mediastinum. The availability of intraoperative PTH aids the decision for surgical exploration and completion.

Reference intervals of spot urine copper excretion in preschool children and potential application in pre-symptomatic screening of Wilson disease

The objectives were to determine the reference intervals of spot urine copper excretion indexes in pre-school children and to evaluate their utility in screening for Wilson disease (WD). With spot urine collected from a control sample of preschool children (aged 3-7 years, n=153), the reference intervals of spot urine copper excretion indexes and their biological variation were defined. In order to investigate their utility performance in screening for WD in this age group, multiple spot urine samples from six WD patients who were diagnosed at presymptomatic stage were also analysed and compared. Cut-off values useful for detection of WD were defined by receiver operator curve (ROC) analysis. Biological (inter-individual) variation of spot urine copper indexes expressed as coefficient of variation (CVg) were around 60% at this age group, which was moderate and similar to other clinically useful urine tests, such as urine albumin excretion ratio. Spot urine copper excretion strongly correlated with both urine creatinine and osmolality. Linear regression against both creatinine and osmolality showed that ∼94% of data points in healthy preschool children fell within the prediction interval, suggesting that both were useful normalisation factors. ROC showed that copper to osmolality ratio was the best index with an area under curve (AUC) greater than 0.98. Cut-off values of 0.5 μmol/L, 0.1 μmol/mmol and 0.00085 μmol/mOsmol (32 μg/L, 56 μg/g creatinine and 0.054 μg/mOsmol, respectively, in conventional units) for spot urine copper concentration, copper to creatinine ratio and copper to osmolality ratio, respectively, have potential application in the differentiation of WD patients. Based on the data, a new WD screening strategy targeting preschool children is proposed. Application of a bivariate screening strategy using spot urine copper concentration and urine osmolality may be useful in a population-wide screening program for WD among preschool children.

The establishment and application of sialoscintigraphic reference values from patients with obstructive sialadenitis.

To evaluate feasibility of establishing a clinically applicable reference value through those unaffected salivary gland on sialoscintigraphic data obtained from patients presented with obstructive sialadenitis affected a single gland. Ninety-one patients suffered from single salivary gland swelling, pain/tenderness and received sialoscintigraphic examinations were retrospectively enrolled. The quantitative data parameters, including the uptake ratio, maximal accumulation, maximal excretion, time to maximal (Tmax) and time to minimal (Tmin) activity of the affected and unaffected glands, were calculated for analysis. Data were also obtained and recorded for comparison from 50 patients who fulfill the American-European criteria for the diagnosis of Sjogren's syndrome. The maximal excretion appeared to be the best indicator for distinguishing affected and unaffected glands of obstructive diseases, for parotid and submandibular glands (P = 0.0002 and P < 0.0001, respectively). The area under the receiver-operating characteristic curve (AUC) is 0.82 for submandibular glands. In patients with Sjogren's syndrome, the maximal excretion and Tmin were the best parameters, for parotid (P = 0.002 and P < 0.0001, respectively) and submandibular glands (P < 0.0001 and P = 0.002, respectively). Uptake ratio was a good parameter for submandibular gland (P < 0.0001). The AUC of maximal excretion and uptake ratio for submandibular glands is 0.81 and 0.77, respectively. Quantitative data obtained from the unaffected glands of patients with obstructive sialadenitis could be used as reference values for the functional evaluation of salivary gland disorders with maximal excretion as one of the reliable parameters.

Ecological Stoichiometery and Consumer-Driven Nutrient Recycling by Elliptio complanata (Lightfoot) in a Northeastern Coastal Zone Pond

Freshwater mussels recycle nutrients within their environment, and the extent of their influence depends on ambient nutrient concentrations and time of year. This study investigated the stoichiometry of consumer-driven nutrient recycling (C, N, and P) of the numerically dominant indigenous freshwater mussel Elliptio complanata (Eastern Elliptio) in a New England pond, which we accomplished by evaluating the stoichiometry of seston, mussel tissues, excretion, and biodeposition. Based on our results, we identified 4 major findings. First, we found seston CNP was not variable across seasons as expected, with only 4 of 10 pairwise interactions being statistically significant, and did not necessarily match the Redfield ratio as expected with higher C:N and lower C:P and N:P observations. Second, we found our tissue CNP to be below the expected 106:16:1 Redfield ratio and that the mussels did not adhere to strict stoichiometric homeostasis throughout different sizes/ages, as shown with 5 of 12 regressions being statistically significant. Third, we found freshwater mussel excretion to be similar to that found in other studies and that excretion rates and ratios were influenced by size and shifted with changes in season—possibly related to seston composition as well as environmental conditions such as temperature, based on 7 of 10 statistical analyzes being significant. Finally, we found freshwater mussel biodeposition to be variable across time for nutrient rates and ratios as we expected.

Pharmacokinetics, Tissue Distribution, and Excretion Study of Cajanonic Acid A in Rats by UPLC-MS/MS.

Cajanonic acid A (CAA), a prenylated stilbene derivative extracted from the leaves of pigeon pea (Cajanus cajan), has been reported to possess inhibitory activity on the peroxisome proliferator-activated receptor gamma (PPARγ) and protein tyrosine phosphatase 1B (PTP1B). Its hypoglycemic activity in rats is comparable to that of the approved antidiabetic agent rosiglitazone. Therefore, CAA is a potential candidate for the treatment of type 2 diabetes and a lead compound for the discovery of novel hypoglycemic drugs. To achieve a thorough understanding of the biological behavior of CAA in vivo, our current study was designed to investigate the pharmacokinetics, bioavailability, distribution, and excretion of CAA in rats by UPLC-MS/MS. Chromatographic separation was performed on BEHC18 column (2.1 mm × 50 mm, 1.7 µm). Quantification was performed under the negative ion mode by using single reaction monitoring (SRM) of the transitions of m/z 353.14 → 309.11 for CAA and m/z 269.86 → 224.11 for genistein, respectively. Standard calibration curve showed excellent linearity (r2 > 0.99) within the range of 2 - 800 ng/mL. The accuracies and precisions were within the acceptance limits (all < 20%). CAA was quickly absorbed into bloodstream and distributed rapidly and widely to various tissues. The excretion ratio of CAA in the 3 main pathways via bile, feces, and urine was only 5.17%. These results indicate that CAA was quickly and thoroughly metabolized in vivo and excreted mainly as metabolites.

Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria.

The clinical effects of alkaptonuria (AKU) are delayed and ageing influences disease progression. Morbidity of AKU is secondary to high circulating homogentisic acid (HGA) and ochronosis. It is not known whether HGA is produced by or processed in the kidney in AKU. Data from AKU patients from four studies were merged to form a single AKU group. A control group of non-AKU subjects was generated by merging data from two non-AKU studies. Data were used to derive renal clearance and fractional excretion (FE) ratios for creatinine, HGA, phenylalanine (PHE) and tyrosine (TYR) using standard calculations, for comparison between the AKU and the control groups. There were 225 AKU patients in the AKU group and 52 in the non-AKU control group. Circulating HGA increased with age (P < 0.001), and was significantly associated with decreased HGA clearance (CLHGA ) (P < 0.001) and FEHGA (P < 0.001). CLHGA and FEHGA were increased beyond the theoretical maximum renal plasma flow, confirming renal production and emphasising the greater contribution of net tubular secretion than glomerular filtration to renal elimination of HGA. The kidneys are crucial to elimination of HGA. Elimination of HGA is impaired with age resulting in worsening disease over time. The kidney is an important site for production of HGA. Tubular secretion of HGA contributes more to elimination of HGA in AKU than glomerular filtration.

Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a Marker of Diabetic Nephropathy in Type 1 Diabetic Patients.

Glomerular and tubulointerstitial damage plays a role in renal function failure in diabetic patients. While both serum and urine levels of neutrophil gelatinase-associated lipocalin (NGAL) show significantly increased levels in acute renal pathologies, the NGAL increase in active phase indicates a reversible condition in chronic cases. 52 type 1 diabetic patients and 30 healthy volunteers participated in the study. The diabetic participants were separated into two groups as follows: a normoalbuminuria group consisting of those with an albumin/creatinine ratio less than 30 mg/g and an albuminuria group consisting of those with an albumin/ creatinine ratio equal or greater than 30 mg/g. Albumin, creatinine and NGAL were measured in all participants. Urinary NGAL median level was 21.1 ng/mL for diabetic patients and 11.9 ng/mL for healthy controls, and the difference between the two groups was statistically significant. When diabetic patients were compared as those with and without albuminuria, the median urinary NGAL levels of normoalbuminuria and albuminuria were 24.7 and 16.1 ng/mL, respectively, but the difference was not statistically significant. Statistically similar results were obtained through evaluation of the ratio of urinary NGAL excretion to creatinine excretion. The NGAL/Cr ratio was significantly higher in diabetic patients than in healthy controls, but no statistically significant difference was found between the diabetic patients with and without albuminuria. Urinary NGAL excretion in type 1 diabetic patients is found to be increased over a wide range, but it does not correlate with urinary albumin excretion. In this regard, urinary NGAL excretion should not be used as an alternative to microalbuminuria in detecting diabetic nephropathy. The greater amount of NGAL excretion among diabetic patients may be due to diabetic nephropathy with possible tubulointerstitial damage pathologies.

Abnormal circadian rhythm of urinary sodium excretion correlates closely with hypertension and target organ damage in Chinese patients with CKD.

Whether the abnormal circadian rhythm of urinary sodium excretion is associated with hypertension in chronic kidney disease (CKD) is poorly understood. In this study, we assessed the relationship between the circadian rhythm of urinary sodium excretion and hypertension. Urinary samples were collected during both the day (07:00 to 22:00) and night (22:00 to 07:00) to estimate night/day urinary sodium excretion ratios. Blood pressure (BP) and clinical data were also measured. A total of 1,099 Chinese CKD patients were recruited, 308 patients were excluded, and 791 patients were final enrolled in this study. Among them, 291 patients were normotensive and 500 were hypertensive CKD patients. A 1:1 propensity score matching (PSM) analysis was performed with age and estimated glomerular filtration rate (eGFR) matched between 190 normotensive and hypertensive patients. In the full cohort and PSM cohort, multivariate regression analysis showed that the night/day urinary sodium excretion ratio was an independent risk factor for clinical hypertension, whereas 24 h urinary sodium excretion, diurnal and nocturnal urinary sodium excretion were not. When the night/day urinary sodium excretion ratios were further divided into tertiles (tertile 1 < 0.47, tertile 2, 0.47-0.84 and tertile 3 > 0.84), multivariate analysis showed that tertile 3 was independently associated with hypertension in the full and PSM cohorts. In addition, tertile 3 was also independently associated with eGFR ≤ 60 mL/min/1.73 m2 and left ventricular hypertrophy. These data suggested that an abnormal circadian rhythm of urinary sodium excretion was independently associated with hypertension and target-organ damage. Individualized salt intake and therapeutic strategies should be used to normalize the natriuretic dipping profile in CKD patients.

Effects of mild and moderate renal dysfunction on pharmacokinetics, pharmacodynamics, and safety of dotinurad: a novel selective urate reabsorption inhibitor

BackgroundDotinurad, a novel selective urate reabsorption inhibitor, exerts a serum uric acid-lowering effect by selectively inhibiting urate transporter 1 (URAT1) in patients with hyperuricemia. It is generally known that the progression of renal dysfunction is associated with a reduction in the serum uric acid-lowering effects of uricosuric drugs. We, therefore, investigated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of dotinurad in subjects with renal dysfunction.MethodsThis was a parallel-group, open-label, single-dose clinical pharmacology study. Dotinurad (1 mg) was administered once, orally to subjects with mild (estimated glomerular filtration rate [eGFR], ≥ 60 to < 90 mL/min/1.73 m2) or moderate (eGFR, ≥ 30 to < 60 mL/min/1.73 m2) renal dysfunction or normal (eGFR, ≥ 90 mL/min/1.73 m2) renal function.ResultsThe time-course of mean plasma concentration of dotinurad had similar profiles across the groups. Regarding PK, there was no significant difference between the renal dysfunction groups and normal renal function group. Regarding PD, the maximum reduction rate in serum uric acid levels and the fractional uric acid excretion (FE) ratio (FE0–24/FE−24–0) were significantly lower in the moderate renal dysfunction group than in the normal renal function group. However, other PD parameters were not significantly different among the groups. No notable adverse events or adverse drug reactions were observed in this study.ConclusionThese results suggested that no dose adjustment might be necessary when administering dotinurad to patients with mild-to-moderate renal dysfunction.ClinicalTrials.gov Identifier: NCT02347046.

Comparative study on metabolic profiling and excretion in rat bile between combination of notoginseng total saponins and safflower total flavonoids and its individual extracts by LC–MS/MS

The combination of notoginseng total saponins (NS) and safflower total flavonoids (SF), namely CNS, presents a synergistic protection effect on the myocardial ischemia rats. The aim of this study was to find the clues for their synergistic actions by comparing the biliary metabolism and excretion profiles after oral administration of CNS and its individual extracts. An ultra-performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometer (UPLC-QTRAP-MS/MS) platform was used to identify and quantify the CNS-derived components in bile. The neutral losses, precursor ions, and predictive multiple reaction monitoring (pMRM) scans were firstly used to detect the CNS-derived ingredients in vivo. A total of 43 components, including 38 flavonoids and 5 ginsenosides were tentatively identified according to the previously established chemical and metabolic profiles of NS and SF. Afterwards, the primary circulating and biological components, hydroxysafflor yellow A (HSYA), ginsenosides Rg1 (GRg1), Re (GRe), and Rd (GRd) were chosen to compare the bile excretion between CNS and its individual extract groups, by using a validated LC-MRM-MS/MS method. The approach was proved to be well satisfied the related requirements from the guidelines of FDA (specificity, calibration curve, sensitivity, precision, accuracy, matrix effect, recovery, and stability). Comparing with the SF and NS groups, the combination group did not affect the metabolic pathways of the CNS-related components, however, it decreased the cumulative excretion ratios of HSYA, GRg1, GRe, and GRd. In conclusion, the compatibility of SF and NS could reduce the bile excretion of the CNS-derived compounds, which may be one of the reasons for the enhancement of anti-myocardial ischemia after combination.

Egestion Versus Excretion: A Meta-Analysis Examining Nutrient Release Rates and Ratios across Freshwater Fauna

In aquatic settings, animals directly affect ecosystem functions through excretion of dissolved nutrients. However, the comparative role of egestion as an animal-mediated nutrient flux remains understudied. We conducted a literature survey and meta-analysis to directly compare nitrogen (N), phosphorus (P), and N:P of egestion compared to excretion rates and ratios across freshwater animals. Synthesizing 215 datasets across 47 animal species (all primary consumers or omnivores), we show that the total N and P egestion rates exceed inorganic N and P excretion rates but not total N and P excretion rates, and that proportions of P egested compared to excreted depend on body size and animal phylum. We further show that variance of egestion rates is often greater than excretion rates, reflecting greater inter-individual and temporal variation of egestion as a nutrient flux in comparison to excretion. At phylogenetic levels, our analysis suggests that Mollusca exhibit the greatest rates and variance of P egestion relative to excretion, especially compared to Arthropoda. Given quantitative evidence of egestion as a dominant and dynamic animal-mediated nutrient flux, our synthesis demonstrates the need for additional studies of rates, stoichiometry, and roles of animal egestion in aquatic settings.

Relationship between aerobic fitness and nephron index in middle-aged and older adults

Background: The preservation of functional nephrons is considerably important for the prevention of the development of renal dysfunction in middle-aged and older adults. Recent clinical and basic studies have shown that the number of functional nephrons can be estimated by the ratio of urinary phosphate excretion to serum fibroblast growth factor 23 (FGF23) levels, defined as the nephron index. However, there are few clinical pieces of evidence regarding the nephron index and strategies for the maintenance of higher levels of nephron index remains unexplored. In the present study, we focused on aerobic fitness which is one of the independent predictors for renal dysfunction and investigated whether aerobic fitness is related to the nephron index in middle-aged and older adults.

Urinary angiotensinogen antedates the development of stage 3 CKD in patients with type 1 diabetes mellitus.

We examined if urinary angiotensinogen (uAOG), a marker of intrarenal renin‐angiotensin system activity, antedates stage 3 chronic kidney disease (CKD) using samples from participants in the Diabetes Control and Complications Trial (DCCT) and later in the Epidemiology of Diabetes Intervention and Complications (EDIC) trial. In a nested case–control design, cases were matched at the outcome visit (eGFR less than 60, 21‐59 mL/min per 1.73 m2) on age, gender, and diabetes duration, with controls: eGFR (95, 75‐119, mL/min per 1.73 m2.) Additionally, in an exploratory analysis progressive renal decline (PRD), defined as eGFR loss >3.5 mL/min per 1.73m2/year, was evaluated using only data from EDIC because no progressions were observed during DCCT. At the EDIC visit, which antedated the GFR outcome visit by 2 years (range 1–7years) the median uAOG/creatinine was markedly higher in cases than in controls (13.9 vs. 3.8 ng/mg P = 0.003) whereas at the DCCT visit, which antedated the GFR outcome by 17 to 20 years it was not (2.75 vs. 3.16 ng/mg, respectively). The Odds Ratio for uAOG and CKD stage 3 development was significant after adjusting for eGFR, HbA1c, and systolic blood pressure 1.82 (1.00–3.29) but no longer significant when Albumin Excretion Ratio (AER) was included 1.21 (0.65–2.24).In the PRD analysis, uAOG/creatinine was sixfold higher in participants who experienced PRD than in those who did not (26 vs. 4.0 ng/mg, P = 0.003). The Odds Ratio for uAOG and PRD was significant after adjusting for eGFR, HbA1c, and systolic blood pressure 2.48 (1.46–4.22) but no longer significant when AER was included 1.32 (0.76–2.30). In people with type1 diabetes, a robust increase in uAOG antedates the development of stage 3 CKD but is not superior to AER in predicting this renal outcome. Increased uAOG moreover is associated with PRD, an index of progression to End Stage Kidney Disease (ESKD).

Investigating intestinal permeability and gut microbiota roles in acute coronary syndrome patients

BackgroundAcute Coronary Syndrome (ACS) is a leading cause of morbidity and mortality. Perturbed gut-microbiota (dysbiosis) and increased intestinal permeability (leaky-gut) with translocation of bacterial antigens, play critical role in obesity and metabolic syndrome, which are also major ACS risk factors. Additionally, Trimethylamine-N-Oxide (TMAO), a metabolite produced by phylum Proteobacteria in gut is implicated in developing ACS. As Proteobacteria is a major source of translocated antigen lipopolysaccharides (LPS), we hypothesized that ACS patients have leaky-gut condition characterized by dysbiosis with increased Proteobacteria, leading to elevated blood levels of TMAO and LPS. MethodsIn a pilot case-control study, we enrolled 19 ACS patients (within 72-h of cardiac events) and 19 healthy-controls. Gut barrier function was determined using lactulose-to-mannitol urinary excretion ratio (L/M ratio). Stool microbiome composition was examined using16S sequencing and predictive functional analysis for LPS biosynthesis pathway by PICRUSt tool. Serum TMAO and LPS levels were measured. ResultsACS patients had increased Gammaproteobacteria compared to controls:1.8 ± 3.0 vs. 0.2 ± 0.4% (P = 0.04). Though Proteobacteria level was increased but not statistically significant: 4.1 ± 3.8 vs. 2.1 ± 1.7% (P = 0.056). L/M-ratio was three times higher in ACS patients; 0.06 ± 0.07 vs 0.023 ± 0.02, (P = 0.014). Surprisingly, there was no difference in the mean serum LPS or TMAO levels. However, PICRUSt analysis indicated increased Proteobacteria population increasingly contributed to LPS biosynthesis in ACS patients only. ConclusionsACS patients likely to have leaky-gut and perturbed gut microbiota. Further studies are required to precisely define the role of dysbiosis in ACS.

Iodine bioavailability from cow milk: a randomized, crossover balance study in healthy iodine-replete adults

Milk and dairy products are considered important dietary sources of iodine in many countries. However, to our knowledge, iodine bioavailability from milk has not been directly measured in humans. The aim of this study was to compare iodine bioavailability in iodine-replete adults from: 1) cow milk containing a high concentration of native iodine; 2) milk containing a low concentration of native iodine, with the addition of potassium iodide (KI) to assess a potential matrix effect; and 3) an aqueous solution of KI as a comparator; with all 3 containing equal amounts of total iodine (263 µg/250 mL). We also speciated iodine in milk. We conducted a 3-wk, randomized, crossover balance study in adults (n=12) consuming directly analyzed, standardized diets. During the 3 test conditions - high intrinsic iodine milk (IIM), extrinsically added iodine in milk (EIM), and aqueous iodine solution (AIS) - subjects collected 24-h urine over 3 d and consumed the test drink on the second day, with 3- or 4-d wash-out periods prior to each treatment. Iodine absorption was calculated as the ratio of urinary iodine excretion (UIE) to total iodine intake. Milk iodine speciation was performed using ion chromatography-mass spectrometry. Iodine intake from the standardized diet was 195±6 µg/d for males and 107±6 µg/d for females; the test drinks provided an additional 263 µg. Eleven subjects completed the protocol. There was a linear relation between iodine intake and UIE (β=0.89, SE=0.04, P<0.001). There were no significant differences in UIE among the 3 conditions (P=0.24). Median (range) fractional iodine absorption across the 3 conditions was 91 (51-145), 72 (48-95), and 98 (51-143)% on days 1, 2, and 3, respectively, with day 2 significantly lower compared with days 1 and 3 (P<0.001). In milk, 80-93% of the total iodine was inorganic iodide. Nearly all of the iodine in cow milk is iodide and although fractional iodine absorption from milk decreases with increasing dose, its bioavailability is high. The trial was registered at clinicaltrials.gov as NCT03590431.